Polysaccharides are highly prevalent in plants and animals, and frequently have important roles in biological structure. Both natural and synthetic polysaccharides may be useful in a wide variety of commercial applications including, for example, in paper products, foodstuffs, hydrogels, thickeners, water treatment applications, encapsulating media, drug delivery, hair treatment, wound healing, skin care, etc., to name a few. Most naturally occurring polysaccharides are built from sugar-based molecules that are connected through glycosidic linkages. Synthetic polysaccharides containing unnatural linkages may also be useful, thereby expanding the role of polysaccharides in both industrial applications and commercial products.
Unnatural linkages may be advantageous in polysaccharides as their incorporation may serve to mediate polymer properties. For example, unnatural linkages may affect crystallinity or solubility in a predictable fashion. Unnatural linkages may also allow for the introduction of derivatizable functionalities in polysaccharides. For example, nitrogen-containing polymers may be readily derivatized by chemical transformations, such as reduction, oxidation, protonation, etc. of the nitrogen-containing functionalities, leading to changes in both electronic and structural features of the polymer. Despite the versatility and potential for nitrogen-containing polymers, polysaccharides having nitrogen functionalities in the polymer backbone are rare and represent a relatively undeveloped field of polymer chemistry.
Methods for polysaccharide synthesis that incorporate unnatural linkages may also facilitate control over the saccharide composition of the polysaccharide product. For instance, unnatural linkages may allow preparation of polysaccharides by assembly of either or both monomeric and oligomeric building blocks. The ability to synthesize new polysaccharides by piecing together monosaccharides, disaccharides, trisaccharides, and/or low molecular weight polysaccharides may lead to greater control over polymer properties and open the door for the synthesis of new materials with mixed linkages.
Whereas a number of strategies for polysaccharide synthesis involving unnatural linkages are known (e.g., Hanessian in, Preparative Carbohydrate Chemistry, Dekker, New York, 1996; and Khan and O'Neill, eds., Modern Methods in Carbohydrate Synthesis, Harwood, Amsterdam, 1996), most of these methods lead to low molecular weight polysaccharides. An exception is a recent work that reports chemoenzymatic synthesis of sugar-containing polymers (Liu, et al., J. Amer. Chem. Soc., 1999, 121, 466). In this article, galactose oxidase is used first to selectively oxidize the −6 on galactose to an aldehyde group. Subsequently, polycondensation of the aldehyde group with an aminosugar via reductive amination affords amine-linked polysaccharides. However, the reported isolated yields in these reactions are relatively low (7-20%), most likely due to the formation of a large amount of low molecular weight oligomeric products.
Presently, among the many methods developed for the synthesis of polysaccharides, the condensation of ketones and aldehydes with aminooxy groups has not been reported as being employed in polymerization reactions. This oxime-forming reaction, however, is well known outside the realm of polymer chemistry (See, e.g., Canne, et al., J. Am. Chem. Soc. 1995, 117, 2998; Lu, et al., J. Am. Chem. Soc. 1996, 118, 8518;. Liu, et al., J. Am. Chem. Soc. 1996, 118, 307; Rodriguez, et al., J. Am. Chem. Soc. 1997, 119, 9905; Cervigni, et al., Angew. Chem. Int. Ed. 1996, 35, 1230; Zhao, et al., Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 1629).
Polysaccharides are versatile and desirable polymers as indicated by their prevalence in numerous industrial applications and commercial embodiments. New polysaccharides may be needed to satisfy the ever-increasing demand for improved materials. The importance of polysaccharides in applications related to, for example, water treatment, paper products, hydrogel wound care, encapsulation, drug delivery, skin care, etc. clearly shows a need for polysaccharides that are stable, non-toxic, amenable to aqueous systems and biocompatible. The large-scale use of polysaccharides also creates a need for their efficient preparation from inexpensive starting materials in environmentally safe solvent systems such as water. Preparative methods involving assembly of different saccharides such as mono-, di-, tri-, and low molecular weight polysaccharides are also desirable and may lead to new polysaccharides having novel compositions and properties. The oxime-linked polysaccharides and their methods of preparation described herein can help fulfill these and other needs.